Cysteine (Cys) and Histidine (His) play a crucial role in human pathologies. Among these, Cysteine acts as an intracellular redox buffer that influence detoxification and critical metabolic functions. Deficiency in Cysteine causes oxidative damage, haematopoiesis, psoriasis, leucocyte loss and metabolic disorders. Higher level of Cysteine in the human blood plasma (HBP) is known to cause cardiovascular and Alzheimer's diseases. Histidine can act as a neurotransmitter in the central nervous system of mammals. Its deficiency could affect human growth factor and may cause the impaired nutritional state of patients with chronic kidney disease. Higher level of Histidine could cause metabolic disorders like histidinemia. Estimation of these levels in blood plasma is essential for understanding the role of these groups in the pathogenesis of vascular diseases, specifically Cysteine and Histidine sensors are required.
Molecular probes are reported for vital biothiols, like cysteine (Cys) and histidine (His), however, examples of molecular probes capable of detecting Cysteine and Histidine in biological fluids in presence of homocysteine (Hcy) and glutathione (GSH) are rather limited. Molecular probes that are generally being used for detection of biothiols either in physiological condition or in biological fluids are mostly based on chemodosimetric reaction and such process often suffers from the relatively large incubation time ranging from 20 minutes to 1 hr or more. Alternate approach utilizes the higher affinity of Cu(II) towards S-donor nucleophiles for designing molecular probes with fluorescence on response. Such reactions mostly happen within millisecond time scale and thus, this methodology has an edge over the other. Among various molecular probes that are specific towards Cysteine without any interference from Hey and GSH and work in pure physiological conditions are rather rare, while such limited probes are known for Histidine.
However, majority of such reagents relied on chemodosimetric detection and estimation of the total thiol content in human blood plasma (HBP). Use of certain fraction of organic solvents was described in most such reports for solubilising the reagent.

Article titled ‘An Highly selective fluorescent recognition of histidine by a crown ether-terpyridine-Zn (II) sensor’ by Jiao Du et. al published in Chem. Commun., 2013, 49, 5399-5401 disclose a Zn (II) complex that exhibits enhanced fluorescence in the presence of histidine but not in the presence of any other amino acids including cysteine. This sensor could also distinguish histidine from other imidazole derivatives.

Article titled “Diimino conjugate of glucosyl-cresol as receptor for Cu2+ and its complex for cysteine and histidine’ by Atanu Mitra et. al. in trends in carbohydrate research, vol 5, no. 4(2013) 20-24 disclose a calorimetric approach for Cu2+ sensing on a Diimino conjugate of glucosyl cresol (L). The chemo sensor (L) with Cu2+ is used for detecting cysteine and histidine by absorption and calorimetric titrations. Further, synthesis of chemo sensor (L) comprises single one step condensation of glucosamine with 2,6-dioxo-4-methyl-1-hydroxy benzene (2) as shown in scheme below:
Complexation of metal ion with dipicolylamine (DPA) ligand as chemical sensors for peptides, amino acids is explored in the art. An article titled ‘Molecular Recognition and Fluorescence Sensing of Monophosphorylated Peptides in Aqueous Solution by Bis(zinc(II)-dipicolylamine)-Based Artificial Receptors’ by Akio Ojida et al. J. Am. Chem. Soc., 2004, 126 (8), pp 2454-2463 fluorescent chemosensors bearing two zinc ions coordinated to distinct dipicolylamine (Dpa) sites. Fluorescence titration experiments show the selective and strong binding toward phosphate derivatives in aqueous solution. The chemosensors showed clear distinction between phosphorylated and nonphosphorylated peptides and strong binding to a negatively charged phosphorylated peptide.
Prior art search reveals that there remains a need in the art for quick and reliable approach for detection of Histidine and Cysteine in aqueous medium or physiological fluids, without the interference of other amino acids or specifically, glutathione.
The promising role of metal ion complex with dipcolylamine crafted on fluorophores which can show ‘turn on’ type fluorescence enhancement encouraged the present inventors to provide novel receptor molecule using novel ligand for selective and instantaneous detection of cysteine and histidine among the ensemble of amino acids under physiological conditions.